Brain Atrophy in Healthy Aging Is Related to CSF Levels of Aβ1-42

Reduced levels of beta-amyloid(1-42) (A beta 1-42) and increased levels of tau proteins in the cerebrospinal fluid (CSF) are found in Alzheimer's disease (AD), likely reflecting A beta deposition in plaques and neuronal and axonal damage. It is not known whether these biomarkers are associated with brain atrophy also in healthy aging. We tested the relationship between CSF levels of A beta 1-42 and tau (total tau and tau phosphorylated at threonine 181) proteins and 1-year brain atrophy in 71 cognitively normal elderly individuals. Results showed that under a certain threshold value, levels of A beta 1-42 correlated highly with 1-year change in a wide range of brain areas. The strongest relationships were not found in the regions most vulnerable early in AD. Above the threshold level, A beta 1-42 was not related to brain changes, but significant volume reductions as well as ventricular expansion were still seen. It is concluded that A beta 1-42 correlates with brain atrophy and ventricular expansion in a subgroup of cognitively normal elderly individuals but that reductions independent of CSF levels of A beta 1-42 is common. Further research and follow-up examinations over several years are needed to test whether degenerative pathology will eventually develop in the group of cognitively normal elderly individuals with low levels of A beta 1-42.